Effects of arzoxifene on bone, lipid markers, and safety parameters in postmenopausal women with low bone mass.

UNLABELLED: In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene's safety profile appeared similar to raloxifene. INTRODUCTION: This 6-month, Phase 2, double-blind, placebo- and raloxifene-controlled study was designed to assess the effects of arzoxifene on bone turnover and overall safety in postmenopausal women with low bone mass. METHODS: Postmenopausal women (N = 219; mean age, 59 years) with a T-score between -1 and -2.5 were randomly assigned to daily arzoxifene 5, 10, 20, or 40 mg, raloxifene 60 mg, or placebo. All received daily calcium. RESULTS: All arzoxifene doses significantly reduced osteocalcin (primary endpoint), type 1 collagen C-telopeptide, bone specific alkaline phosphatase, and procollagen type I amino-terminal propeptide versus placebo, and increased lumbar spine BMD. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene. Arzoxifene decreased cholesterol, low-density lipoprotein cholesterol, and fibrinogen versus placebo. Endometrial thickness change with arzoxifene was not significantly different from placebo or raloxifene; no cases of endometrial hyperplasia or adenocarcinoma were observed. Adverse event reporting with arzoxifene was similar to that with raloxifene, as were hot flush and night sweat reporting. CONCLUSIONS: Arzoxifene suppressed bone turnover and increased BMD. Within the limitations of this study, the endometrial safety profile of arzoxifene appeared similar to that of raloxifene. While no clear dose effect was evident, arzoxifene 20 and 40 mg/day appeared the optimal doses for reducing bone turnover.

Ground water discharge and the related nutrient and trace metal fluxes into Quincy bay, Massachusetts.

Measurement of the rate and direction of ground water flow beneath Wollaston Beach, Quincy, Massachusetts by use of a heat-pulsing flowmeter shows a mean velocity in the bulk sediment of 40 cm d(-1). The estimated total discharge of ground water into Quincy Bay during October 1990 was 1324-2177 m(3) d(-1), a relatively low ground water discharge rate. The tides have only a moderate effect on the rate and direction of this flow. Other important controls on the rate and volume of ground water flow are the limited thickness, geographic extent, and permeability of the aquifer. Comparisons of published streamflow data and estimates of ground water discharge indicate that ground water makes up between 7.4-12.1% of the gaged freshwater input into Quincy Bay. The data from this study suggest the ground water discharge is a less important recharge component to Quincy Bay than predicted by National Urban Runoff Program (NURP) models.The high nitrate and low nitrite and ammonia concentrations in the ground water at the backshore well sites and low nitrate and high nitrite and ammonia concentrations in the water flowing from the foreshore suggests that denitrification is active in the sediments. The low ground water flow rates and low nitrate concentrations in the foreshore samples suggest that little or no nitrate is surviving the denitrification process to affect the planktonic community. Similarly, oxidizing conditions in the aquifer and low trace metal concentrations in the ground water samples suggest that the metals may be precipitating and binding to sedimentary phases before impacting the bay.

Effects of oral amines on the EEG.

Oral tyramine activated pre-existing episodic EEG abnormalities--namely, sharp waves, spike and wave, and localised theta activity--in epileptic patients. Little change was found in the EEGs of migrainous subjects after chocolate or beta-phenylethylamine. The implications of the findings with tyramine are discussed.

Effect of chocolate in migraine: a double-blind study.

The effect of chocolate on a group of volunteer migrainous subjects, who had observed that headache regularly occurred after the ingestion of small amounts of cocoa products, was investigated. Two separate studies were carried out in a double-blind placebo controlled manner. Only 13 headaches occurred to chocolate alone in 80 subject sessions, and only two subjects responded consistently to chocolate in the two studies. This suggests that chocolate on its own is rarely a precipitant of migraine. Other possible implications of the results are also discussed.